FORTY-FIRST ANNUAL REPORT · Title of Study I Clinical Drug Trial Protocol . Assessment of Impairment ofVascular Function in Rats by Environmental Exposure to Marijuana Second Hand

·-·-----~ --~-- ~------- -- ----- -------------

FORTY-FIRST ANNUAL REPORT

of the

RESEARCH ADVISORY PANEL OF CALIFORNIA

2011·

PREPARED FOR THE

LEGISLATURE AND GOVERNOR


455 Golden Gate Avenue- Suite 11000 San Francisco, California 94102-7004

www.ag.ca.gov/research

TABLE OF CONTENTS

Page

LIST OF 2011 PANEL MEMBERS 2

SUMMARY OF 2011 PANEL ACTIVITIES 3

SELECTED RESEARCH FINDINGS 3

TABLE 1- Research Studies approved in 2011 7

TABLE 2 - Research Studies closed in 2011 17

APPENDICES

Appendix A - Currently Open Schedule I and II 25 Non-Human & Academic Human Studies

Appendix B - Currently Open Schedule II 31 Clinical Drug Tfial Studies

Appendix C - Currently Open Research Studies 43 on the Treatment of Controlled Substance Abuse

Appendix D - Pertinent Sections - California Health and Safety Code

§ 11213 -Persons and researches using controlled substances 45 § 11480 & 11481 - Research Advisory Panel 45 § 11603 & 11604 - Attorney General 46 § 24172- Experimental subject's bill ofrights 47 § 241 73 - Informed consent 48

2011 PANEL MEMBERS


Edward P. O'Brien, J.D. Panel Chairman Appointed by Attorney General

Y. Jennifer Ahn, Pharm.D. Executive Officer

Robert Quandt, Jr., Pharm.D. Consultant

Andrew S. Kayser,, MD, PhD Appointed by the University of California at San Francisco Designated University of California

John Mendelson, M.D. Appointed by the California Medical Association Designated professional medical society

Michele Pato, M.D. Appointed by the University of Southern California Designated private university

Laurence R. Upjohn, Pharm.D. Appointed by the Department of Public Health

Sheri VanOsdol, ~harm.D.

Appointed by the State Board of Pharmacy

RAPC Website: www.ag.ca.gov/research

E-mail contact: [email protected]

This report represents a consensus among Panel members acting as individual experts. It does not represent policies or positions of the appointing agencies nor have those agencies been consulted by the Panel during its function or during the preparation of this report.

2

SUMMARY OF 2011 PANEL ACTIVITIES

During 2011 the Panel reviewed forty-three research study submissions. Forty-one were approved by the Panel. Among forty-one approved studies, eleven studies were Academic research studies, three studies were Substance Abuse Treatment research protocols, and twenty-seven studies were Clinical Drug Trial research protocols.

Thirty-seven research studies were completed or, in a few cases, terminated in 2011, and they were closed on the Panel's records.

At the end of2011, the Panel was monitoring ninety-seven active research projects. Note Appendices A, B, and C for specific listings. '

As part of the Panel's supervisory responsibility, ongoing projects are monitored by means of annual reports, Significant Adverse Event (SAE) reports and site visits. Approval may be withdrawn if the study deviates significantly from the approved protocol.

Table 1 is a list of the studies approved by the Panel in 2011 and Table 2 is a list of the studies closed by the Panel in 2011.

SELECTED RESEARCH FINDINGS

Below are brief summary reports of several Panel approved projects which are of interest and indicative ofthe types of controlled substance research projects currently ongoing in California:

Titan Pharmaceuticals has announced positive results of six-month open-label safety retreatment study ofprobuphine titled "A Phase 3, Six-Month, Open-Label ReTreatment Study ofProbuphine™ in Opioid Addiction"

A total of 85 patients were enrolled at 18 sites with 67 subjects completing treatment. In California, 33 subjects were enrolled, 26 subjects completed the study, and 7 subjects withdrew early.

In this study, Probuphine was shown to be well tolerated, including the implant insertion and removal procedures, with a low incidence of adverse events and overall safety profile similar to that observed in the confirmatory Phase 3 study. Patients also reported a decreased use of illicit opioids, good control of opioid withdrawal and cravings and

3

high overall satisfaction with Probuphine. These data build upon the positive results of the Probuphine Phase 3 program reported to date and further support the company's preparation of a New Drug Application (NDA) for Probuphine.

Titan also provided an update on the preparation of the NDA for Probuphine, which it now plans to submit in the third quarter of this year. The company is on track to complete its analytical testing ofProbuphine to provide additional Chemistry, ·Manufacturing and Control (CMC) data requested bythe U.S. Food and Drug Administration (FDA) along with its preparation of the integrated clinical data, summary reports and electronic document preparation by mid-year. The manufacturing facility expansion and qualification for commercial scale production fo Probuphine is in process, but has been slightly delayed due to longer than expected lead-time on air handling equipment and the manufacturing of three qualification batches is now expected to be completed in September.

Dr. Peggy Compton, RN, PhD, FAAN and colleagues at University of California, Los Angeles have provided the Panel with the following summary of research titled "Pain, Opioids and Pro-inflammatory Immune Responses"

The goal of our study is to evaluate inflammatory and immune responses to pain and/or opiate challenges in prescription opioid abusers (N=22, 11 female) and gender and agematched healthy controls. To get the study underway and establish study procedures, we obtained UCLA IRB approval (MIRB3) for the healthy control group in June of 2010. To date, of the 163 potential healthy control subjects (78 females) responding to recruitment efforts, 45 (20 females) have been screened and 20 enrolled (9 females).

We submitted an amendment to include buprenorphine-maintained prescription opioid abusers (POAs) in December 2010 and were granted approval to enroll three POAs on May 26, 2011. IRB approval for the remaining eighteen POAs is contingent upon the IRB's satisfaction with the participation report of these initial3 POAs. Since recruitment efforts began in July of2011, we've had eight potential POA respondents (2 females), all ofwhom did not meet the initial eligibility criteria of being an opioid abuser or in a buprenorphine treatment program.

Decreased POA admission rates at the Integrated Substance Abuse Programs clinic was an initial barrier to out POA recruiting efforts. In August of2011 the IRB approved expansion of our recruitment efforts to include SAMHSA-qualified opioid treatment centers (OTC) and private buprenorphine treatment specialist clinics in the greater Los Angeles area. Despite positive clinician response to our study objectives, we have yet to enroll a POA subject. Our colleagues have cited our exclusion criteria prohibiting participation of subjects with co-morbid DSM-IV diagnoses as a significant barrier to

4

recruitment; the clinical reality is that the majority of opioid abusers who present to treatment have a dual-diagnosis. We continue to explore ways to boost recruitment and enrollment. Encouraged by the many positive clinician responses, we remain optimistic that we will reach our target of POAs by August 31,2012.

Rhodes Pharmaceuticals has reported the status of the study titled "A Randomized, Parallel, Double-Blind Efficacy and Safety study ofBiphentin™ Methylphenidate Hydrochloride Extended Release Capsules Compared to Placebo in Children and Adolescents 6 to 18 Years With Attention Deficit Hyperactivity Disorder"

Biphentin™ is designed to be a single, daily dose alternative to separate doses of immediate release methylphenidate by providing an extended release biphasic plasma profile. It distinguishes itself from similar extended release products on the market by achieving a first Cmax more similar to immediate release methylphenidate, which provides clinical advantages. It also comes in more strengths, eight, that allow better individualized dosing. Biphentin® was approved by Health Canada in March 2006 and launched in Canada in August 2006.

One California sate was involved in this multi-center clinical trial at the University of California, Irvine Child Development Center. The UC Irvine site enrolled 29 subjects, and 24 subjects completed the 12-week study. The first subject was enrolled in January 2011. The clinical phase of the study concluded in November 2011.

The protocol provides for continuing compassionate use of the study drug following termination of the 12-week study. Currently approximately 14 patients continue to take the drug, one capsule a day. These patients are being monitored on a periodic basis.

5

~-~--~------~-----~

6

TABLE 1

RESEARCH STUDIES APPROVED IN 2011

PI/ Sponsor Title of Study I Clinical Drug

Hussien Al-Shamma, Ph.D. Arena Pharmaceuticals, Inc. San Diego, CA

Reese T. Jones, M.D. UCSF Drug Dependence Research Center San Francisco, CA

Daniel Levin, Ph.D. N orac Pharma Azusa, CA

Sean Mackey, MD, PhD Stanford University Division of Pain Management Palo Alto, CA

Ardis Ann Moe, M.D. UCLA Center for AIDS Research and Education Los Angeles, CA

Loren H. Parsons, Ph.D. The Scripps Research Institute La Jolla, CA

Trial Protocol

Evaluation of lorcaserin for abuse liability using the Drug Discrimination test in the Rat

Phase I Study of Interactions between Oral Naltrexone and Bupropion and Intravenous Methamphetamine in Methamphetamine Experienced

Evaluation of Cannabinoids derived from the Natural Product Marijuana

Neural and Immune Effects of Short-term Opioid Use in Chronic Pain Patients

Phase III, Placebo-Controlled, Double-Blind Crossover Study of Slow-Release Methylphenidate (Concerta ™) for Treatment of HIV Dementia

Cognitive and Neurochemical Effects of J'-.,.9tetrahydrocannabinol and related cannabinoids in rodents

7

Table 1 Cont.

PI/ Sponsor

Matthew L. Springer, Ph.D. UCSF San Francisco, CA

Michael A. Taffe, Ph.D. The Scripps Research Institute La Jolla, CA

Michael A. Taffe, Ph.D. The Scripps Research Institute La Jolla, CA

Ronald G. Victor, M.D. Cedars-Sinai Medical Center Los Angeles, CA

Barth Wilsey, M.D. UC Davis Sacramento, CA

AcelRx Pharmaceuticals Redwood City, CA

Title of Study I Clinical Drug Trial Protocol

Assessment of Impairment of Vascular Function in Rats by Environmental Exposure to Marijuana Second Hand Smoke

Behavioral and Physiological Toxicities of Cannabinoids

Behavioral Toxicities of Amphetamine and Cathinone Stimulant Drugs

Cocaine and Sympathetic Nerve Activity in Humans - "Cocaine and the Heart"

The Effect of Vaporized Cannabis on Neuropathic Pain in Spinal Cord Injury

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of the Sufentanil NanoTab for the Management of Acute Pain Following Bunionectomy Alone or with Hammertoe Repair (AcelRx SAP202)

8

PI/ Sponsor



Astra Zeneca I CRO - Quintiles Overland Park, KS


Table I Cont.


A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of the Sufentanil NanoTab PCA System/15 meg for the Treatment of Post-Operative in Patients after Open Abdominal Surgery . (AcelRx IAP31 0)

A Multicenter, Randomized, Open-Label, Parallel-Group Trial to Compare the Efficacy and Safety of the Sufentanil NanoTab PCA System/15 meg to Intravenous PatientControlled Analgesia with Morphine for the Treatment of Acute Post-Operative Pain (AcelRx IAP309)

A Randomized, Double-Blind, PlaceboControlled Study to Assess the Efficacy and Safety ofNKTR-118 in Patients with NonCancer-Related Pain and Opioid-Induced Constipation (OIC) (AstraZeneca D3820C00004)

A Randomized, Double-Blind, PlaceboControlled Study to Assess the Efficacy and Safety ofNKTR-118 in Patients with NonCancer-Related Pain and Opioid-Induced Constipation (OIC) (AstraZeneca D3 820C00005)

9

Table 1 Cont.

PI/ Sponsor






A Randomized, Double-Blind, PlaceboControlled Study to Assess the Efficacy and Safety ofNKTR-11_8 in Relieving OpioidInduced Constipation (OIC) in Patients with Cancer-Related Pain (AstraZeneca D3820C00006)

A Randomized, Double-Blind, PlaceboControlled 12-Week Extension Study to

· Assess the Safety and Tolerability ofNKTR118 in Patients with Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC) (AstraZeneca D3820C00007)

An Open-Label 52 week Study to Assess the Long-Term Safety ofNKTR-118 in OpioidInduced Constipation (OIC) in Patients with Non-Cancer-Related Pain (AstraZeneca D3820C00008)

An Open-label, Parallel-group, Phase I Study to Compare the Pharmacokinetics ofNKTR118 Following a Single-Oral Dose in Subjects with Renal Impairment and Subjects with Normal Renal Function (AstraZenica D3820C00009)

10

---- --···-~-------·--- ·----

Table 1 Cont.

PI/ Sponsor

Johnson & Johnson PRD Malvern, PA

Mallinckrodt Inc I CRO- INC Middleton, WI

Mallinckrodt Inc. Hazelwood, MD

Mundipharma I CRO - Parexel Woburn,MA


A Single-Dose, Open-Label, Randomized, Four-Way Crossover Study to Assess the Dose-Proportionality of the Pharmacokinetics ofTapentadol, Given as Tamper-Resistant Tablets, in Healthy Japanese and Korean Male Subjects (J & J PAl 1064)

An Open Label Safety Study of COV795 in Subjects with Osteoarthritis or Chronic Low Back Pain (COV 15000181US)

A Phase 3, Multicenter, Randomized, DoubleBlind, Placebo-Controlled, Parallel-Group Evaluation of the Safety and Analgesic Efficacy of COV795 (Oxycodone HCl I Acetaminophen) ER Tablets in Moderate to Severe Post-Operative Bunionectomy Pain Followed by an Open Label Extension (COV 15000182US)

A Confirmatory, Placebo-Controlled, Randomized, Double-Blind, Single-Dummy, Parallel Group, Ratio-Finding Study in Constipated Pain Patients to Establish an Optimal Hydromorphone (Mundipharma HMX 3501)

11

Table 1 Cont.

PI/ Sponsor

N ovartis Pharmaceuticals East Hanover, NJ

Purdue I CRO - PRA Raleigh, NC

Purdue I CRO - Quintiles Overland Park, KS


A 6-Month, Open-Label Extension to a 40Week, Randomized, Double-Blind, PlaceboControlled, Multicenter Efficacy and Safety study ofRitalin® LA in the Treatment of Adult Patients with Childhood-Onset ADHD (Novartis CRIT 124 D 23 02E1)

A Randomized, Double-blind, Placebocontrolled, Multicenter Trial with an Enriched Study Design to Assess the Efficacy and Safety of Oxycodone/Naloxone Controlledrelease Tablets (OXN) Compared to Placebo in Opioid-experienced Subjects with Moderate to Severe Pain due to Chronic Low Back Pain who Require Around-the-clock Opioid Therapy (Purdue ONU3701)

A Randomized, Double-blind, Doubledummy, Placebo-controlled, Activecontrolled, Parallel-group, Multicenter Trial of Oxycodone Naloxone Controlled-release Tablets (OXN) to Assess the Analgesic Efficacy (Compared to Placebo) and the Management of Opioid-induced Constipation (Compared to Oxycodone Controlled-release Tablets (OXY) in Opioid-experienced Subjects with Uncontrolled Moderate to Severe Chronic Low Back Pain and a History of Opioid-induced Constipation who Require Around-the-clock Opioid Therapy (Purdue ONU3704)

12

'--------------------- ----~----- ---------------------

PI/ Sponsor


Purdue I CRO - INC Raleigh, NC

Purdue I CRO. - PRA Charlottesville, VA

Table 1 Cont.


A Randomized, Double-blind, Doubledummy, Placebo-controlled, Activecontrolled, Parallel-group, Multicenter Trial of Oxycodone/Naloxone Controlled-release Tablets OXN) to Assess the Anafgesic Efficacy (Compared to Placebo) and the · Management of Opioid-induced Constipation (Compared to Oxycodone Controlled-release. Tablets (OXY) in Opioid-experienced Subjects with Controlled Moderate to Severe Chronic Low Back Pain and a History of Opioid-induced Constipation with Require Around-the-clock Opioid Therapy (Purdue ONU3705)

An Open-label, Multicenter Study to Assess the Long-Term Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Oncedaily in Subjects with Moderate to Severe Chronic Non-malignant and Non-neuropathic Pain (Purdue HYD3003)

An Open-label, Extension Study to Assess the Long-Term Safety of Twice Daily Oxycodone Hydrochloride Controlled-release Tablets in Opioid Experienced Children Who Completed the OTR3001 Study (Purdue OTR3002)

13

Table 1 Cont.

PI/ Sponsor


Roxane I CRO - Quintiles Durham, NC

Shire I CRO - Premier Research Bluff City, TN

Shire / CRO - ICON Brentwood, TN


A Multicenter, Randomized, Double-blind, Placebo-controlled Study with an Open-label Run-in to Assess the Efficacy and Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects with Moderate to Severe Chronic Low Back Pain (Purdue HYD3002)

A Multicenter, Open Label, Safety and Pharmacokinetic Study of Oral Morphine Sulfate Administration in Pediatric Subjects 2 years old through 17 years old with Postoperative Pain (Roxane MORP-OS+T-(2-17)-SPK-1)

A Phase 2, Multicenter, Randomized, DoubleBlind, Parallel-Group, Placebo-Controlled, Forced-Dose Titration Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults Aged 18-55 Years with Binge Eating Disorder (Shire SPD489-208)

Phase 3, Multicenter, Randomized, Doubleblind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment ofAdults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with an Antidepressant (Shire SPD489-322)

14

Table 1 Cont.

PI/ Sponsor

Shire I CRO - ICON Brentwood, TN


Shire Pharmaceuticals Wayne, PA


Phase 3, Multicenter, Randomized, Doubleblind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment of Adults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with an Antidepressant (Shire SPD489-323)

Phase 3, Open-label, Multicenter, 12-month Extension Safety and Tolerability Study of SPD489 in Combination with an Antidepressant in the Treatment of Adults with Major Depressive Disorder with Residual Symptoms or Inadequate Response Following Treatment with an Antidepressant (Shire SPD489-329)

A Phase 1, Randomized, Double-blind, . Placebo-controlled Study to Assess the Safety,

Tolerability, Pharmacokinetics, and Pharmacodynamics ofAscending, Multiple Oral Doses of SPD489 (Lisdexamfetamine Dimesylate) in Clinically Stable Adults with Schizophrenia (Shire SPD489-119)

15

Table 1 Cont.

PI/ Sponsor

Shire Pharmaceuticals Wayne,PA

Lara Ray, Ph.D. UCLA Los Angeles, CA

Steve Shoptaw, Ph.D. UCLA Dept of Family Medicine Los Angeles, CA

NIDA Rockville, MD


A Phase 2, Multicenter, Double-blind, Parallel-group, Randomized, Placebocontrolled, Forced-dose Titration, Doseranging Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment of Adults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with an Antidepressant (Shire SPD 489-209)

Pharmacogenetics ofNaltrexone for Methamphetamine Use Disorder

V arenicline for Methamphetamine Dependence

Cocaine Use Reduction with Buprenorphine (CURB) (NIDA C1N-0048)

16

TABLE2

RESEARCH STUDIES CLOSED OR CANCELLED IN 2011

Sponsor I PI Title of Study I Clinical Drug Trial Protocol

Gayle C. Baldwin, Ph.D. Methamphetamine Dependence: A Novel UCLA Laboratory Model Los Angeles, CA

Giovanni Cucchiaro, MD Caudal versus Intrathecal Morphine for Childrens Hospital Los Angeles Post-operative Pain Control in Pediatric USC Keck School ofMedicine Patients. Los Angeles, CA

G. Patrick Dauert, M.D. Does Oral Methadone Use in Opiate UC Davis Medical Center Replacement Therapy Prolong the QTc Sacramento, CA Interval?

Robert H. Edwards, M.D. Role of glutamate release by monoamine Departments ofNeurology and Physiology neurons UCSF School ofMedicine San Francisco, CA

Frederick :p. Frankel, Ph.D. Social Skills Training for Medicated UCLA Children Los Angeles, CA

Jean Gehricke, Ph.D. The Reinforcing Mechanisms of Smoking UC Irvine in Adult ADHD Irvine, CA

17

Table 2 Cont.

Sponsor I PI

Ian Gibbons, Ph.D. Theranos, Inc. Palo Alto, CA

Scott Irwin, MD, PhD San Diego Hospice and Institute for Palliative Medicine San Diego, CA

Thomas S. Kilduff, Ph.D. SRI International Menlo Park, CA

Thomas King, Ph.D. Alexza Pharmaceuticals Mt. View, CA

·Yuriy Kirichok, Ph.D. UCSF San Francisco, CA

Edward T. Kisak, Ph.D. F qubed, Inc. San Diego, CA

Kimberly D. Lakes, Ph.D. UC Irvine Irvine, CA


Assay Development for Medical Device Submission to FDA

An Open Label Trial of Methylphenidate for The Rapid Treatment of Depression in Hospice Patients

Neurobiological Studies of Gammahydroxybutyrate (GHB)

Development of an FDA Approved Dronabinol Pharmaceutical Product for Inhalation Delivery

Effects of Cannabinoids on Sperm Activity and Fertility

Transdermal Delivery of . Tetrahydrocannabinol

The Effects ofVyvanse on Brain Hemodynamics and Reading

18

-------- ----·-····-···----·- .

------ ---- - -- -----------

Sponsor I PI

Stanley Parsons, Ph.D. UC Santa Barbara Santa Barbara, CA

Mark Rollins, MD, PhD UCSF San Francisco, CA

Cephalon, Inc. Fort Washington, P A

Cephalon, Inc. Fort Washington, P A

Eli Lilly Pharmaceuticals Indianapolis, IN

Table 2 Cont.


Rapid Detection of 4-hydroxybutyrate

Supplemental Oxygen: A Reduction in Pulse Oximetry Sensitivity or an Increased Margin of Safety?

A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours for Relief of Moderate to Severe Pain in Patients with Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time (Cephalon C33237/3079).

A 12-Month, Open-Label Study to Evaluate the Long-Term Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90mg Every 12 Hours in Patients Who Require Opioid Treatment for an Extended Period of Time (Cephalon C33237/3080)

A Fixed-Dose, Randomized, DoubleBlind, Placebo-Controlled Study of L Y2216684 in Pediatric Patients with Attention Deficit/Hyperactivity Disorder (Lilly H9P-MC-LNBF)

19

Table 2 Cont.

Sponsor I PI

Insys Therapeutics Phoenix, AZ

Ortho-McNeil Janssen Scientific Affairs Titusville, NJ

Johnson & Johnson PRD Horsham, PA

Johnson & Johnson PRD Titusville, NJ


A Randomized, Double-Blind, PlaceboControlled Multi-Center Study to Evaluate the Safety and Efficacy of Fentanyl Sublingual Spray (Fentanyl SL Spray) for the Treatment of Breakthrough Cancer Pain (Insys INS-05-00 1)

A Placebo-controlled, Double-blind, Parallel-group, Individualized Dosing Study Optimizing Treatment of Adults with Attention Deficit Hyperactivity Disorder to an Effective Response with OROS Methylphenidate (OMJSA CONCERTA.:ATT-3014)

An Open-Label, Single-Ascending-Dose Study to Investigate the Pharmacokinetics and Safety ofCONCERTA® in Healthy Japanese Adult Male Subjects (J&J CONCERTANAP1003)

A Randomized, Double-Blind, Placeboand Active-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of JNJ-42160443 as Monotherapy in Subjects with Moderate to Severe, Chronic Knee pain from Osteoarthritis (J & J PRD JNJ-42160443-PAI-2006)

20

Sponsor I PI

King Pharmaceuticals Cary,NC

N euromed Pharmaceuticals Conshohocken, P A


Table 2 Cont.


A Multi-center, Primary Care-Based, Open-Label Study to Assess the Success of Converting Opioid-Experienced Patients, with Chronic, Moderate to Severe Pain, to EMBEDA™ Using a Standardized Conversion Guide, and to Identify Behaviors Related to Prescription Opioid Abuse, Misuse, and Diversion (King AL0-01-1 0-4003)

A Phase III, Flexible-Dose Titration Followed by a Randomized Double-Blind Study of Controlled-Release OROS® Hydromorphone HCl (NMED-1 077) CompG!Ied to Placebo in Patients with Osteoarthritis Pain (Neuromed NMT1077-302)

Arandomized, multi-center, double-blind, placebo-controlled, cross-over study evaluating the safety and efficacy of Focalin-XR 30 mg vs Focalin XR 20 mg as measured by SKAMP-Combined scores in children with Attention-Deficit Hyperactivity Disorder (ADHD) in a laboratory classroom setting (N ovartis CRIT 124 EUS 21)

21

Table 2 Cont.

Sponsor/ PI

Ortho-McNeil Janssen Scientific Affairs Irvine, CA

Ortho-McNeil Janssen Scientific Affairs Raritan, NJ

QRxPharma I CRO - Rho, Inc. Chapel Hill, NC


Double-Blind, Randomized, PlaceboControlled, Crossover Study Evaluating the Academic, Behavioral and Cognitive Effects ofCONCERTA on Older Children with ADHD (The ABC Study) (OMJSA CONCERTA-ATT-4069)

A Randomized, Double-Blind, MultiCenter, Parallel-Group Study of Tapentadol Immediate Release (IR) vs. Oxycodone IR for the Treatment of Subjects with Acute Post-Operative Pain Following Elective Arthroscopic Shoulder Surgery (OMJSA R331333-PAI-3022)

A Double-Blind, Randomized, MultiCenter, Repeat-Dose, Comparison of the Analgesic Efficacy & Safety of the Opioid Combination Q8003 to each of the Individual Milligram Components (Oxycodone & Morphine) in the Management of Acute Moderate to Severe Pain Following Bunionectomy Surgery (QRxPharma Q8003-021)

22

Table 2 Cont.

Sponsor I PI Title of Study I Clinical Drug Trial Protocol

QRxPharma I CRO - Rho, Inc. Chapel Hill, NC

Shire I CRO- INC Raleigh, NC

Shire I CRO - INC Raleigh, NC

A Randomized, Double-Blind, Multicenter, Repeat-Dose Comparison of Q8003 to the Morphine-Equivalent Doses of Oxycodone and of Morphine for the Opioid-Related Adverse Events of Nausea, Emesis, and Dizziness in Subjects with Acute Moderate-to-Severe Postoperative ·pain Following Bunionectomy Surgery (QRxPharma Q8003-022)

A Phase II, Multicenter Study with Openlabel and Randomized Double-blind Placebo-Controlled Withdrawal Phases to . Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults with Schizophrenia and Predominant Negative Symptoms Who Are Clinically Stable and Taking Stable Doses of Atypical · Antipsychotic Medication (Shire SPD489-204)

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults with Clinically Significant, Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder (Shire SPD-205)

23

Table 2 Cont.

Sponsor /PI

Zogenix, Inc. Emeryville, CA

Gantt Galloway, Pharm.D. APRL CPMC Research Institute San Francisco, CA

Walter Ling, M.D. · UCLA Los Angeles, CA

Catalyst Pharmaceuticals Coral Gables, FL

Catalyst Pharmaceuticals Coral Gables, FL

Titan Pharmaceuticals S. San Francisco, CA


A Randomized Double-Blind, PlaceboControlled Trial to Evaluate the Efficacy, Tolerability and Safety ofHydrocodone Bitartrate Controlled-Release Capsules in Opioid-experienced Subjects with Moderate to Severe Chronic Low Back Pain. (Zogenix ZX002-080 1)

A Dose Ranging Study of Guanfacine for Methamphetamine

Optimizing Outcomes Using Suboxone for Opiate Dependence

Vigabatrin for Treatment of Cocaine Dependence: A Phase II Study" (Catalyst CPP-01005)

Vigabatrin for Treatment of Methamphetamine Dependence: A Phase II Study (Catalyst CPP-02001)

A Phase 3, Six-Month, Open-Label ReTreatment Study ofProbuphine in Opioid Addiction (Titan PR0-811)

24

APPENDIX A

CURRENTLY OPEN (through December 31, 2011) SCHEDULE I AND SCHEDULE II

NON-HUMAN AND ACADEMIC HUMAN RESEARCH STUDIES

Principal Investigator

Mark A. Agius, M.D. UC. Davis Davis, CA

Hussien Al-Shamma, Ph.D. Arena Pharmaceuticals San Diego, CA

Danilyn Angeles, Ph.D. Lorna Linda University Lorna Linda, CA

Mariusz Banaszczyk, Ph.D. Biosite Diagnostics San Marcos, CA

Selena E. Barrett, Ph.D. Ernest Gallo Clinic & Research Ctr. Emeryville, CA

Matthias Behrends, M.D. UCSF San Francisco, CA

Title of Study

Cannabis for Spasticity/Tremor in MS: Placebo Controlled Study

Evaluation of lorcaserin for abuse liability using the Drug Discrimination Test in the Rat

Panel Approved Research

Development of In-vitro Immunoassays for the Detection of Abused Substances

The role of cannabinoids and ibogaine in the treatment of alcoholism and drug addiction

A Randomized, Parallel, Double-Blind Efficacy and Safety Study of Biphentin™ Methylphenidate Hydrochloride Extended Release Capsules Compared to Placebo in Children and Adolescents 6 to 18 years with Attention Deficit Hyperactivity Disorder

25

Appendix A Cont.


Nancy E. Buckley, Ph.D. California State Polytechnic Univ. Pomona, CA 91768

John R. Cashman, Ph.D. Human BioMolecular Research Institute San Diego, CA

KentS. Chu, Ph.D. YJ Bio-Products Cordova, CA

Laura Colin Biostride, Inc. Redwood City, CA

PeggyCompton, RN, PhD UCLA School ofNursing Los Angeles, CA

Mark Geyer, Ph.D. UC San Diego San Diego, CA

Valerie Gruber, Ph.D. UCSF SF General Hospital San Francisco, CA ·

Kanthi F. Hettiarachchi, Ph.D. SRI International Menlo Park, CA

Title of Study

Panel approved research

Molecular Evolution of Human Cocaine Catalysis

Immunochromatographic Test Device for THC and LSD

Panel Approved Research Project

Pain, Opioids, and Pro-inflammatory Immune Responses

Behavioral and Cytoflourimetric Studies of Psychoactive Drugs in Rats

Investigation of Age Differences in Analgesic, Cognitive, and subjective effects of Oxycodone, Hydrocodone, and Acetaminophen

Analysis of Cannabinoids

26


Scott A. Irwin, MD, PhD San Diego Hospice/ Palliative Care San Diego, CA

Reese Jones, M.D. UCSF San Francisco, CA

Adam Leventhal, Ph.D. USC Keck School of Medicine Alhambra, CA

Daniel Levin, Ph.D. NORAC Pharma Azusa, CA




Marie Lin, Ph.D. R.Ph. Lin-Zhi International, Inc. · Sunnyvale, CA

Appendix ACont.

Title of Study


Phase I Study of Interactions between Oral Naltrexone and Bupropion and Intravenous Methamphetamine in Methamphetamine Experienced

Influence of Genes and Emotions on medication Effects





Lin-Zhi Immunoassay Development Study

27

Appendix A Cont.


Edythe London, Ph.D .. UCLA Los Angeles, CA

Sean Mackey, MD, PhD Stanford University Palo Alto, CA

Sean D. McAllister, Ph.D. CPMC Research Institute San Francisco, CA

James T. McCracken, M.D. UCLANPI Los Angeles, CA

John Mendelson, M.D. APRL/CPMC Research Institute San Francisco, CA

John Mendelson, M.D. APRL/CPMC Research Institute San Francisco, CA

Ardis Moe, Ph.D. UCLA Center for AIDS Research Los Angeles, CA

'------ ----·-·----------------

Title of Study

A Study to Assess.the Cardiovascular, Cognitive, and Subjective Effects of Atomoxetine in Combination with Intravenous Amphetamine

Neural and Immune Effects of Short-term Opioid Use in Chronic Pain Patients·


An 8-Week, Randomized, Double-Blind Comparison of Twice-Daily Guanfacine, Once-Daily d-Methylphenidate ER (Focalin XR) and the Combination, with a 12 Month Open-Label Extension for the Treatment of ADHD in Pediatric Subjects Aged 7 to 14 years

The Effects of MDMA on Sleep Architecture, Water Homeostasis, and Cognitive Function

Bioavailability and Urinary Excretion of Oral L-Methamphetamine

Phase III, Placebo-Controlled, Double-Blind Crossover Study of Slow-Release Methylphenidate (Concerta ™) for Treatment of HIV Dementia

28


Loren Parsons, Ph.D. The Scripps Research Institute La Jolla, CA

Richard Reznichek, M.D. Harbor-UCLA Medical Center Torrance, CA

Rajkumar J. Sevak, Ph.D. UCLA Los Angeles, CA

Rajkumar J. Sevak, Ph.D. UCLA Los Angeles, CA

Matthew L. Springer, Ph.D. UCSF San Francisco, CA

Michael Taffe, Ph.D. The Scripps Research Institute La Jolla, CA

Michael Taffe, Ph.D. The Scripps Research Institute La Jolla, CA

Appendix A Cont.

Title of Study

Cognitive and Neurochemical Effects of !.l9tetrahydrocannabinol and related cannabinoids in rodents

A prospective, randomized, double-blind study comparing the efficacy and safety of intra nasal fentanyl spray to placebo as an analgesic in patients undergoing outpatient cystoscopic procedures

Human Methamphetamine Self-Administration in a Progressive-Ratio Paradigm

. Safety and Initial Efficacy of Lisdexamfetamine for Modifying the Behavioral Effects of Intravenous Methamphetamine in Humans

Assessment of Impairment of Vascular Function in Rats by Environmental Exposure to Marijuana Second Hand Smoke

Behavioral and Physiological Toxicities of Cannabinoids

Behavioral Toxicities of Amphetamine and Cathinone Stimulant Drugs

29

--- ----·--~-- ---~

Appendix A Cont.


Stephen Van Dien, Ph.D. Genomatica, Inc. San Diego, CA

Ronald Victor, M.D. Heart Institute Cedars-Sinai Medical Center Los Angeles, CA

Mark Wallace, M.D. UC San Diego San Diego, CA

Jennifer L. Whistler, Ph.D. Ernest Gallo Clinic & Research Ctr. Emeryville, CA

Timothy Wigal, Ph.D. UC Irvine Irvine, CA

Barth Wilsey, M.D. UC Davis Medical Center Sacramento, CA

Barth Wilsey, M.D. UC Davis Medical Center Sacramento, CA

Title of Study


Cocaine and Sympathetic Nerve Activity in Humans - "Cocaine and the Heart"

Efficacy of Inhaled Cannabis for the Treatment of Painful Diabetic Peripheral Neuropathy

Endocytosis and Opioid Receptors

Brain Dopamine Function in Adults with Attention Deficit/Hyperactivity Disorder (ADHD)

The Analgesic Effect of Vaporized Cannabis on Neuropathic Pain

The Effect of Vaporized Cannabis on Neuropathic Pain in Spinal Cord Injury

30

APPENDIXB

CURRENTLY OPEN (through December 31, 2011) SCHEDULE II CLINICAL DRUG TRIAL STUDIES

Sponsor

AcelRx Redwood City, CA



Astra Zenica I CRO - Quintiles Overland Park, KS

Description or Title of Clinical Drug Trial Protocol

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of the Sufentanil NanoTab for the Management of Acute Pain Following Bunionectomy Alone or with Hammertoe Repair (AcelRx SAP202)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of the Sufentanil NanoTab PCA System/15 meg for the Treatment of Post-Operative in Patients after Open Abdominal Surgery (AcelRx IAP310)

A Multicenter, Randomized, Open-Label, Parallel-Group Trial to Compare the Efficacy and Safety of the Sufentanil NanoTab PCA System/15 meg to Intravenous PatientControlled Analgesia with Morphine for the Treatment of Acute Post-Operative Pain (AcelRx IAP309)

A Randomized, Double-Blind, PlaceboControlled Study to Assess the Efficacy and Safety ofNKTR-118 in Patients with NonCancer-Related Pain and Opioid-Induced Constipation (OIC) (AstraZeneca D3820C00004)

31

Sponsor







A Randomized, Double-Blind, PlaceboControlled Study to Assess the Efficacy and Safety ofNKTR-118 in Patients with NonCancer-Related Pain and Opioid-Induced Constipation (OIC) (AstraZeneca D3 820C00005)

A Randomized, Double-Blind, PlaceboControlled Study to Assess the Efficacy and Safety ofNKTR-118 in Relieving OpioidInduced Constipation (OIC) in Patients with Cancer-Related Pain (AstraZeneca D3820C00006)

A Randomized, Double-Blind, PlaceboControlled 12-Week Extension Study to Assess the Safety and Tolerability ofNKTR118 in Patients with Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC) (AstraZeneca D3820C00007)

An Open-Label 52 week Study to Assess the Long-Term Safety ofNKTR-118 in OpioidInduced Constipation (OIC) in Patients with Non-Cancer-Related Pain (AstraZeneca D3820C00008)

An Open-label, Parallel-group, Phase I Study to Compare the Pharmacokinetics ofNKTR118 Following a Single-Oral Dose in Subjects with Renal Impairment and Subjects with Normal Renal Function (AstraZenica D3820C00009)

32

'-----~----------- --~- --~------

Sponsor

BRC Operations Pty Ltd. Ultimo, NSW, Australia

G W Pharmaceuticals Mill Valley, CA

G W Pharmaceuticals Milly Valley, CA

GW Pharmaceuticals Milly Valley, CA

INTRuST Clinical Consortium La Jolla, CA

Johnson & Johnson Titusville, NJ


International Study to Predict Optimized Treatment in Attention Deficit/.Hyperactivity Disorder (BRC iSPOT -A)




Randomized Controlled Trial of Galantamine, Methylphenidate, and Placebo for the Treatment of Cognitive Symptoms in Patients with Mild Traumatic Brain Injury (mTBI) and/or Posttraumatic Stress Disorder (PISD) ("Cognitive REmediation After Trauma

Exposure" Trial = CREATE Trial")

A Randomized-Withdrawal, PlaceboControlled, Study Evaluating the Efficacy, Safety, and Tolerability, of Tapentadol Extended-Release (ER) in Subjects with Chronic, Painful Diabetic Peripheral Neuropathy (DPN) (J&J R331333-PAI-3027)

33

---- -- ----------- -- -------- -----------------------------------

Sponsor

Johnson & Johnson Malvern, PA



Mallinckrodt I CRO - INC Middleton, MD


A Single-Dose, Open-Label, Randomized, Two-Way Crossover Study to Assess the Bioequivalence of Tapentadol Give as Two 25mg Extended-Release Tamper-Resistant Formulation (TRF) Tablets Relative to One 50mg Extended-Release TRF Tablet in Healthy Japanese Male Subjects (J & J R331333 PAl 1062)

A Single-Dose, Open-Label, Randomized, Two-Way Crossover Study to Assess the Bioequivalence of Tapentadol Given as Two 50mg Extended-Release Tamper-Resistant Formulation (TRF) Tablets Relative to One 100mg Extended-Release TRF Tablet in Healthy Japanese Male Subjects (J & J R331333 PAl 1 063)

A Single-Dose, Open-Label, Randomized, Four-Way Crossover Study to Assess the Dose-Proportionality of the Pharmacokinetics ofTapentadol, Given as Tamper-Resistant Tablets, in Healthy Japanese and Korean Male Subjects (J & J PAl 1064)

An Open Label Safety Study of COV795 in Subjects with Osteoarthritis or Chronic Low Back Pain (COV l5000181US)

34

Sponsor

Mallinckrodt Hazelwood, MD

Mundipharma I CRO - Parexel Woburn,MA




A Phase 3, Multicenter, Randomized, DoubleBlind, Placebo-Controlled, Parallel-Group Evaluation of the Safety and Analgesic Efficacy of COV795 (Oxycodone HCl I Acetaminophen) ER Tablets in Moderate to Severe Post-Operative Bunionectomy Pain Followed by an Open Label Extension (COV15000 182US)

A Confirmatory, Placebo-Controlled, Randomized, Double-Blind, Single-Dummy, Parallel Group, Ratio-Finding Study in Constipated Pain Patients to Establish an Optimal Hydromorphone (Mundipharma HMX 3501)

A 40-Week, Randomized, Double-Blind, Placebo controlled, Multicenter Efficacy and Safety Study of Ritalin® LA in the Treatment ofAdult Patients with Childhood-Onset ADHD (Novartis CRIT124D2302)

A 6-Month, Open-Label Extension to a 40Week, Randomized, Double-Blind, PlaceboControlled, Multicenter Efficacy and Safety study of Ritalin® LA in the Treatment of Adult Patients with Childhood-Onset ADHD (Novartis CRIT 124D 2302El)

35

Sponsor

Purdue I CRO - PRA Lenexa, KS

Purdue I CRO - PRA Lenexa, KS

Purdue I CRO - PRA Raleigh, NC


An Open-Label Study to Characterize the . Pharmacokinetics and Safety of Oxycodone HCl q12h Controlled-Release (ORF) Tablets in Pediatric Patients Aged 6 to 16 Years Inclusive, Who Require Opioid Analgesia (Purdue OTR 1 020)

An Open-Label, Multicenter Study ofthe Safety of Twice Daily Oxycodone HCl Controlled-Release Tablets in Opioid Experienced Children from Ages 6 to 16 Years Old, Inclusive, with Moderate to Severe Malignant and/or Nonmalignant Pain Requiring Opioid Analgesics (Purdue OTR 3001)

A Randomized, Double-blind, Placebocontrolled, Multicenter Trial with an Enriched Study Design to Assess the Efficacy and Safety of Oxycodone/N aloxone Controlledrelease Tablets (OXN) Compared to Placebo in Opioid-experienced Subjects with Moderate to Severe Pain due to Chronic Low Back Pain who Require Around-the-clock Opioid Therapy (Purdue ONU3701)

36

Sponsor





A Randomized, Double-blind, Doubledummy, Placebo-controlled, Activecontrolled, Parallel-group, Multicenter Trial of Oxycodone Naloxone Controlled-release Tablets (OXN) to Assess the Analgesic Efficacy (Compared to Placebo) and the Management of Opioid-induced Constipation (Compared to Oxycodone Controlled-release Tablets (OXY) in Opioid-experienced Subjects with Uncontrolled Moderate to Severe Chronic Low Back Pain and a History of Opioid-induced Constipation who Require Around-the-clock Opioid Therapy (Purdue O:NU3704)

A Randomized, Double-blind, Doubledummy, Placebo-controlled, Activecontrolled, Parallel-group, Multicenter Trial of Oxycodone/Naloxone Controlled-release Tablets OXN) to Assess the Analgesic Efficacy (Compared to Placebo) and the Management of Opioid-induced Constipation (Compared to Oxycodone Controlled-release Tablets (OXY) in Opioid-experienced Subjects with Controlled Moderate to Severe Chronic Low Back Pain and a History of Opioid-induced Constipation with Require Around-the-clock Opioid Therapy (Purdue ONU3705)

An Open-label, Multicenter Study to Assess the Long-Term Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Oncedaily in Subjects with Moderate to Severe Chronic Non-malignant and Non-neuropathic Pain (Purdue HYD3003)

37

Sponsor

Purdue I CRO - PRA Charlottesville, VA


Rhodes Pharmaceuticals Boston, MA

Rhodes Pharmaceuticals Boston, MA


An Open-label, Extension Study to Assess the Long-Term Safety of Twice Daily Oxycodone Hydrochloride Controlled-release Tablets in Opioid Experienced Children Who Completed the OTR3001 Study (Purdue OTR3002)

A Multicenter, Randomized, Double-blind, Placebo-controlled Study with an Open-label Run-in to Assess the Efficacy and Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects with Moderate to Severe Chronic Low Back Pain (Purdue HYD3002)

A Randomized, Double-Blind Study ofthe Time Course of Response ofBiphentin® Methylphenidate Hydrochloride Extended Release Capsules As Compared to Placebo in Children 6 to 12 Years With Attention Deficit Hyperactivity Disorder in an Analog Classroom Setting (_R4odes RP-BP-EF001)

A Randomized, Parallel, Double-Blind Efficacy and Safety Study ofBiphentin™ Methylphenidate· Hydrochloride Extended Release Capsules Compared to Placebo in Children and Adolescents 6 to 18 years with Attention Deficit Hyperactivity Disorder (Rhodes RP-BP-EF002)

38

Sponsor

Roxane I CRO - Quintiles Durham,NC

Shire Pharmaceuticals Hampshire, UK


Shire I CRO - Premier BuffCity, TN


A Multicenter, Open Label, Safety and Pharmacokinetic Study of Oral Morphine Sulfate Administration in Pediatric Subjects 2 years old through 17 years old with Postoperative Pain (Roxane MORP-OS+T-(2-17)-SPK-1)

A Phase III, Double-Blind, PlaceboControlled, Randomized Withdrawal, Multicenter, Extension, Safety and Efficacy Study of Lisdexamfetamine Dimesylate (LDX) in Children and Adolescents Aged 617 with Attention-Deficit/Hyperactivity Disorder (ADHD) (Shire SPD489-326)

A Phase 2, Multicenter, Randomized, Doubleblind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults with Clinically Significant, Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder (Shire SPD-205)

A Phase 2, Multicenter, Randomized, DoubleBlind, Parallel-Group, Placebo-Controlled, Forced-Dose Titration Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults Aged 18-55 Years with Binge Eating Disorder (Shire SPD489-208)

39

-~·------·~-· --------~

-~~---~~-

Sponsor





Phase 3, Multicenter, Randomized, Doubleblind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment ofAdults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with an Antidepressant {Shire SPD489-322)

Phase 3, Multicenter, Randomized, Doubleblind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment of Adults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with an Antidepressant (Shire SPD489-323)

Phase 3, Open-label, Multicenter, 12-month Extension Safety and Tolerability Study of

· SPD489 in Combination with an Antidepressant in the Treatment ofAdults with Major Depressive Disorder with Residual Symptoms or Inadequate Response Following Treatment with an Antidepressant (Shire SPD489-329)

40

I

i.

Sponsor


I. Shire Pharmaceuticals

I

Wayne, PA

Zogenix Inc. Emeryville


A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics ofAscending, Multiple Oral Doses of SPD489 (Lisdexamfetamine Dimesylate) in Clinically Stable Adults with Schizophrenia (Shire SPD489-119)

A Phase 2, Multicenter, Double-blind, Parallel-group,- Randomized, Placebocontrolled, Forced-dose Titration, Doseranging Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment of Adults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with a11 Antidepressant (Shire SPD 489-209)

A Long-Term Open-Label Safety Study of Hydrocodone Bitartrate Controlled-Release Capsules with Flexible Dosing to Treat Subjects with Moderate to Severe Pain. (Zogenix ZX002-0802)

41

- -----·-· ---

42

----~---~ --- - --

APPENDIXC

CURRENTLY OPEN (December 31, 2011) RESEARCH STUDIES ON THE TREATMENT OF CONTROLLED SUBSTANCE ABUSE

Description or Title Investigator or Sponsor ofResearch Study

Keith E. Flower, M.D. A Pilot Trial ofNaltrexone for APRL/CPMC Research Institute Methamphetamine Addiction - Role of the San Francisco, CA A118G SNP

Gantt P. Galloway, Pharm.D. A Dose Ranging Study of Modafinil for APRL/CPMC Research Institute Methamphetamine Dependence San Francisco, CA

~ I

Keith Heinzerling, MD, MPH Pharmacogenomics and Medication UCLAISAP Development for Methamphetamine Los Angeles, CA Dependence

Keith Heinzerling, MD, MPH Pilot Trial ofBupropion versus Placebo for UCLAISAP Methamphetamine Abuse in Adolescents Los Angeles, CA

Walter Ling, M.D. Sustained-Release Methylphenidate for UCLAISAP management of Methamphetamine Los Angeles, CA Dependence

Lara Ray, Ph.D. Pharmacogenetics ofNaltrexone for UCLA Methamphetamine Use Disorder Los Angeles, CA

Steven Shoptaw, Ph.D. Phase I Safety Interaction Trial of Ibudilast UCLA. with Methamphetamine Los Angeles, CA

43

Investigator or Sponsor

·Steven Shoptaw, Ph.D. UCLA. Los Angeles, CA

NIDA Rockville, MD ·

Titan Pharmaceuticals I CRO - PPD S. San Francisco, CA

I ·~ i

Description or Title of Research Study

V arenicline for Methamphetamine Dependence

Cocaine Use Reduction with Buprenorphine (CURB) (CTN-0048)

A Randomized, Placebo and ActiveControlled, Multi-Center Study ofProbuphine in Patients with Opioid Dependence (Titan PR0-806)

44

---------·--

APPENDIXD

SECTIONS CONCERNING THE RESEARCH ADVISORY PANEL FROM THE CALIFORNIA HEALTH AND SAFETY CODE

§ 11213. Persons who, under applicable federal laws or regulations, are lawfully entitled to use controlled substances for the purpose of research, instruction, or analysis, may lawfully obtain and use for such purposes such substances as are defined as controlled substances in this division, upon approval for use of such controlled substances in bona fide research, instruction, or analysis by the Research Advisory Panel established pursuant to § 11480 and § 11481.

Such research, instruction, or analysis shall be carried on only under the auspices of the head of a research project which has been approved by the Research Advisory Panel pursuant to § 11480 or § 11481. Complete records of receipts, stocks at hand, and use of these controlled substances shall be kept.

§ 11480. The Legislature finds that there is a need to encourage further research into the nature and effects of marijuana and hallucinogenic drugs and to coordinate research efforts on such subjects.

There is a Research Advisory Panel which consists of a representative of the State Department of Health Services, a representative of the California State Board of Pharmacy, a representative ofthe Attorney General, a representative of the University of California who shall be a pharmacologist, a physician, or a person holding a doctorate degree in the health sciences, a representative of a private university in this State who shall be a pharmacologist, a physician, or a person holding a doctorate degree in the health sciences, a representative of a statewide professional medical society in this state who shall be engaged in the private practice of medicine and shall be experienced in treating controlled substance dependency, a representative appointed by and serving at the pleasure of the Governor who shall have experience in drug abuse, cancer, or controlled substance research and who is either a registered nurse, licensed pursuant to Chapter 6 (commencing with§ 2700) ofDivision 2 of the Business and Professions Code, or other health professional. The Governor shall annually designate the private university and the professional medical society represented on the Panel. Members of the Panel shall be appointed by the heads of the entities to be represented, and they shall serve at the pleasure of the appointing power.

The Panel shall annually select a chairinan from among its members.

45

----

Appendix D Cont.

§ 11480. Cont.

The Panel may hold hearings on, and in other ways study, research projects concerning marijuana or hallucinogenic drugs in this state. Members of the Panel shall serve without compensation, but shall be reimbursed for any actual and necessary expenses incurred in connection with the performance of their duties.

The Panel may approve research projects, which have been registered by the Attorney General, into the nature and effects of marijuana or hallucinogenic drugs, and shall inform the Attorney General of the head of the approved research projects which are entitled to receive quantities of marijuana pursuant to § 114 78.

The Panel may withdraw approval of a research project at any time, and when approval is withdrawn shall notify the head of the research project to return any quantities of marijuana to the Attorney General.

The Panel shall report annually to the Legislature and the Governor those research projects approved by the Panel, the nature of each research project, and, where available, the conclusions ofthe research project.

§ 11481. The Research Advisory Panel may hold hearings on, and in other ways study, research projects concerning the treatment of abuse of controlled substances.

The Panel may approve research projects, which have been registered by the Attorney General, concerning the treatment of abuse of controlled substances and shall inform the chief of such approval. The Panel may withdraw approval of a research project at any time and when approval is withdrawn shall so notify the chief.

The Panel shall, annually and in the manner determined by the Panel, report to the Legislature and the Governor those research projects approved by the Panel, the nature of each research project, and where available, the conclusions ofthe research project.

§ 11603. The Attorney General, with the approval ofthe Research Advisory Panel, may authorize persons engaged in research on the use and effects of controlled substances to withhold the names and other identifying characteristics of individuals who are the subjects of the research. Persons who obtain this authorization are not compelled in any civil, criminal, administrative, legislative, or other proceedings to identify the individuals who are the subjects of research for which the authorization was obtained.

46

~ ---- ------ ~~

Appendix D Cont.

§ 11604. The Attorney General, with the approval of the Research Advisory Panel, may authorize the possession and distribution of controlled substances by persons engaged in research. Persons who obtain this authorization are exempt from state prosecution for possession and distribution of controlled substances to the extent of the authorization.

§ 24172. Experimental subject's bill ofrights; contents

As used in the chapter, "experimental subject's bill of rights," means a list ofthe rights of a subject in a medical experiment, written in a language in which the subject is fluent. Except as otherwise provided in§ 24175, this list shall include, but not be limited to the subject's right to:

(a) Be informed of the nature and purpose of the experiment.

(b) Be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized.

(c) Be given a description of any attendant discomforts and risks reasonably to be expected from the experiment.

(d) Be given an explanation of any benefits to the subject reasonably to be expected from the experiment, if applicable.

(e) Be given a disclosure of any appropriate alternative procedures, drugs or devices that might be advantageous to the subject, and their relative risks and benefits.

(f) Be informed of the avenues of medical treatment, if any, available to the subject after the experiment if complications should arise.

(g) Be given an opportunity to ask any questions concerning the experiment or the procedures involved.

(h) Be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation in the medical experiment without prejudice.

47

- - -- -·- ----

Appendix D Cont.

§ 24172. Cont.

(i) Be given a copy of the signed and dated written consent form as provided for by § 24173 or § 24178.

G) Be given the opportunity to decide to consent or not to consent to a medical · experiment without the intervention of any element of force, fraud, deceit, duress, coercion, or undue influence on the subject's decision.

§ 24173. Informed consent

As used in this chapter, "informed consent" means the authorization given pursuant to § 2417 5 to have a medical experiment performed after each of the following conditions have been satisfied:

(a) The subject or subject's conservator or guardian, or other representative, as specified in§ 24175, is provided with a copy of the experimental subject's bill of rights, prior to consenting to participate in any medical experiment, containing all the information required by§ 24172, and the copy is signed and dated by the subject or the subject's conservator or guardian, or other representative, as specified in§ 24175.

(b) A written consent form is signed and dated by the subject or the subject's conservator or guardian, or other representative, as specified in§ 24175.

(c) The subject or subject's conservator or guardian, or other representative, as specified in§ 24175, is informed both verbally and within the written consent form, in nontechnical terms and in a language in which the subject or the subject's conservator or guardian, or other representative, as specified in§ 24175, is fluent, ofthe following facts of the proposed medical experiment, which might influence the decision to undergo the experiment, including, but not limited to:

(1) An explanation of the procedures to be followed in the medical experiment and any drug or device to be utilized, including the purposes of the procedures, drugs, or devices. If a placebo is to be administered or dispensed to a portion of the subjects involved in a medical experiment, all subjects of the experiment shall be informed of that fact; however, they need not be informed as to whether they will actually be administered or dispensed a placebo.

48

-----------

Appendix D Cont.

§ 24173. Cont.

(2) A description of any attendant discomfort and risks to the subject reasonably to be expected.

(3) An explanation of any benefits to the subject reasonably to be expected, if applicable.

(4) A disclosure of any appropriate alternative procedures, drugs, or devices that might be advantageous to the subject, and their relative risks and benefits.

(5) An estimate of the expected recovery time of the subject after the experiment.

(6) An offer to answer any inquiries concerning the experiment or the procedures involved.

(7) An instruction to the subject that he or she is free to withdraw his or her prior consent to the medical experiment and discontinue participation in the medical · experiment at any time, without prejudice to the subject.

(8) The name, institutional affiliation, if any, and address of the person or persons actually performing and primarily responsible for the conduct of the experiment.

(9) The name of the sponsor or funding source, if any, or manufacturer if the experiment involves a drug or device, and the organization, if any, under whose general aegis the experiment is being conducted.

(1 0) The name, address, and phone number of an impartial third party, not associated with the experiment, to whom the subject may address complaints about the experiment.

(11) The material financial stake or interest, if any, that the investigator or research institution has in the outcome of the medical experiment. For purposes of this section, "material" means ten thousand dollars ($10,000) or more in securities or other assets valued at the date of disclosure, or in relevant cumulative salary or other income, regardless ofwhen it is earned or expected to be earned.

49

----~~~~-

Appendix D Cont.

§ 24173. Cont.

(d) The written consent form is signed and dated by any person other than the subject or the conservator or guardian, or other representative of the subject, as specified in § 241 7 5, who can attest that the requirements for informed consent to the medical experiment have been satisfied.

(e) Consent is voluntary and freely given by the human subject or the conservator or guardian, or other representative, as specified by§ 24175, without the intervention of any element of force, fraud, deceit, duress, coercion, or undue influence.

50

Documents

FORTY-FIRST ANNUAL REPORT · Title of Study I Clinical Drug Trial Protocol . Assessment of Impairment ofVascular Function in Rats by Environmental Exposure to Marijuana Second Hand